Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta Outbreak Among Fully Vaccinated Nursing Home Residents Likely Initiated by a Fully Vaccinated Staff Member - Connecticut, July-August 2021.

During July-August 2021, a coronavirus disease 2019 (COVID-19) outbreak involving 21 residents (all fully vaccinated) and 10 staff (9 fully vaccinated) occurred in a Connecticut nursing home. The outbreak was likely initiated by a fully vaccinated staff member and propagated by fully vaccinated persons. Prior COVID-19 was protective among vaccinated residents.

The Ca2+-gated channel TMEM16A amplifies capillary pericyte contraction and reduces cerebral blood flow after ischemia.

Pericyte-mediated capillary constriction decreases cerebral blood flow in stroke after an occluded artery is unblocked. The determinants of pericyte tone are poorly understood. We show that a small rise in cytoplasmic Ca2+ concentration ([Ca2+]i) in pericytes activated chloride efflux through the Ca2+-gated anion channel TMEM16A, thus depolarizing the cell and opening voltage-gated calcium channels. This mechanism strongly amplified the pericyte [Ca2+]i rise and capillary constriction evoked by contractile agonists and ischemia. In a rodent stroke model, TMEM16A inhibition slowed the ischemia-evoked pericyte [Ca2+]i rise, capillary constriction, and pericyte death; reduced neutrophil stalling; and improved cerebrovascular reperfusion. Genetic analysis implicated altered TMEM16A expression in poor patient recovery from ischemic stroke. Thus, pericyte TMEM16A is a crucial regulator of cerebral capillary function and a potential therapeutic target for stroke and possibly other disorders of impaired microvascular flow, such as Alzheimer's disease and vascular dementia.

A 90-second magnetocardiogram using a novel analysis system to assess for coronary artery stenosis in Emergency department observation unit chest pain patients.

BACKGROUND: Magnetocardiography (MCG) has been shown to non-invasively detect coronary artery stenosis (CAS). Emergency department (ED) patients with possible acute coronary syndrome (ACS) are commonly placed in an observation unit (OU) for further evaluation. Our objective was to compare a novel MCG analysis system with stress testing (ST) and/or coronary angiography (CA) in non-high risk EDOU chest pain patients. METHODS: This is a prospective pilot study of non-high risk EDOU chest pain patients evaluated with ST and/or CA that underwent a resting 90-second MCG scan between August 2017 and February 2018. A positive MCG scan was defined as having current dipole deviations with dispersion or splitting during the repolarization phase. ST, CA and major adverse cardiac events (MACE) 30 days and 6 months post-discharge assessed. RESULTS: Of 101 study patients, mean age was 56 years and 53.6% were male. MCG scan sensitivity with 95% CI was 27.3% [7.3%, 60.7%], specificity 77.8% [67.5%, 85.6%], PPV 13.0% [3.4%, 34.7%] and NPV 89.7% [80.3%, 95.2%] compared to ST, and 33.3% [7.5%, 70.7%], 78.3% [68.4%, 86.2%], 13% [5.2%, 29.0%] and 92.3% [88.2%, 95.1%] respectively compared to ST and CA. No patients had positive ST, CA or MACE 30 days and 6 months post-discharge. CONCLUSION: This pilot study suggests a resting 90-second MCG scan shows promise in evaluating EDOU chest pain patients for CAS and warrants further study as an alternative testing modality to identify patients safe for discharge. Larger studies are needed to assess accuracy of MCG using this novel analysis system.

MesA, a novel fungal protein required for the stabilization of polarity axes in Aspergillus nidulans.

The Aspergillus nidulans proteome possesses a single formin, SepA, which is required for actin ring formation at septation sites and also plays a role in polarized morphogenesis. Previous observations imply that complex regulatory mechanisms control the function of SepA and ensure its correct localization within hyphal tip cells. To characterize these mechanisms, we undertook a screen for mutations that enhance sepA defects. Of the mutants recovered, mesA1 causes the most dramatic defect in polarity establishment when SepA function is compromised. In a wild-type background, mesA1 mutants undergo aberrant hyphal morphogenesis, whereas septum formation remains unaffected. Molecular characterization revealed that MesA is a novel fungal protein that contains predicted transmembrane domains and localizes to hyphal tips. We show that MesA promotes the localized assembly of actin cables at polarization sites by facilitating the stable recruitment of SepA. We also provide evidence that MesA may regulate the formation or distribution of sterol-rich membrane domains. Our results suggest that these domains may be part of novel mechanism that directs SepA to hyphal tips.

Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases.

Human BSEP (ABCB11) mutations are the molecular basis for at least three clinical forms of liver disease, progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), and intrahepatic cholestasis of pregnancy (ICP). To better understand the pathobiology of these disease phenotypes, we hypothesized that different mutations may cause significant differences in protein defects. Therefore we compared the effect of two PFIC2 mutations (D482G, E297G) with two BRIC2 mutations (A570T and R1050C) and one ICP mutation (N591S) with regard to the subcellular localization, maturation, and function of the rat Bsep protein. Bile salt transport was retained in all but the E297G mutant. Mutant proteins were expressed at reduced levels on the plasma membrane of transfected HEK293 cells compared with wild-type (WT) Bsep in the following order: WT > N591S > R1050C approximately A570T approximately E297G >> D482G. Total cell protein and surface protein expression were reduced to the same extent, suggesting that trafficking of these mutants to the plasma membrane is not impaired. All Bsep mutants accumulate in perinuclear aggresome-like structures in the presence of the proteasome inhibitor MG-132, suggesting that mutations are associated with protein instability and ubiquitin-dependent degradation. Reduced temperature, sodium butyrate, and sodium 4-phenylbutyrate enhanced the expression of the mature and cell surface D482G protein in HEK293 cells. These results suggest that the clinical phenotypes of PFIC2, BRIC2, and ICP may directly correlate with the amount of mature protein that is expressed at the cell surface and that strategies to stabilize cell surface mutant protein may be therapeutic.